Kd. Thrall et Dv. Kenny, EVALUATION OF A CARBON-TETRACHLORIDE PHYSIOLOGICALLY-BASED PHARMACOKINETIC MODEL USING REAL-TIME BREATH-ANALYSIS MONITORING OF THE RAT, Inhalation toxicology, 8(3), 1996, pp. 251-261
A methodology has been developed to monitor the exhalation of volatile
compounds in rats in a real-time manner. The exhalation data is colle
cted using an innovative breath-analysis system that links the exhaled
breath from the rat directly with a mass spectrometer. Because the br
eath-analysis system generates a new data point approximately every se
cond, this methodology can aid in describing the rapid exponential emp
tying of the blood compartment that occurs immediately following peak
exposure. Furthermore, coupling the real-time collection of biokinetic
data with a physiologically descriptive toxicokinetic model should be
useful in elucidating complex in situ chemical-mediated biological re
actions, particularly for rapidly occurring processes. The utility of
this new methodology is illustrated using carbon tetrachloride (CCl4)
as a demonstration compound. An existing physiologically based pharmac
okinetic (PBPK) model was taken from the literature and modified to si
mulate an intravenous route of CCl4 exposure in the male Fischer 344 r
at. This PBPK model for the rat accurately described the concentration
s of CCl4 in real-time exhaled breath data collected from rats exposed
to CCl4 via a single intravenous injection.